沙格列汀片与安立泽~片在中国健康受试者中单次给药的生物等效性研究

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英文篇名：Bioequivalence study of single-dose saxagliptin table verus Onglyza~ table in Chinese health subjects 作者：王进 ; 陈刚 ; 王泽娟 ; 刘英 ; 漆璐 ; 刘晓娜 ; 刘晨 ; 王瑜 ; 雷春璞 ; 刘慧娟 ; 王兴河 英文作者：WANG Jin;CHEN Gang;WANG Ze-juan;LIU Ying;QI Lu;LIU Xiao-na;LIU Chen;WANG Yu;LEI Chun-pu;LIU Hui-juan;WANG Xing-he;Phase Ⅰ Clinical Centre,Beijing Shijitan Hospital,Capital Medical University; 关键词：沙格列汀片 ; 安立泽片 ; 生物等效性研究 英文关键词：saxagliptin table;;Onglyza~ table;;bioequivalence 中文刊名：ZXYZ 英文刊名：Chinese Journal of New Drugs 机构：首都医科大学附属北京世纪坛医院药物Ⅰ期研究室; 出版日期：2019-01-15 出版单位：中国新药杂志 年：2019 期：v.28 语种：中文; 页：ZXYZ201901011 页数：5 CN：01 ISSN：11-2850/R 分类号：64-68

摘要

目的:评价江苏奥赛康药业股份有限公司研制生产的沙格列汀片5 mg(受试制剂)与中美(上海)施贵宝制药有限公司生产的原研药沙格列汀片5 mg(商品名:安立泽~,参比制剂)在中国健康受试者中的生物等效性和安全性。方法:采用单中心、开放、随机、双周期交叉的试验设计,共入组48例中国健康受试者,包括空腹组(24例)和餐后组(24例)。采用WinNolin 6. 4软件计算药动学参数。结果:空腹组和餐后组分别有23例和21例受试者的血药浓度-时间数据进行了药动学分析和生物等效分析。空腹组受试制剂和参比制剂的血浆原形沙格列汀主要药动学参数:t1/2分别为(3. 56±1. 52)和(3. 70±1. 28) h; Tmax分别为0. 587 h(中位值:0. 5 h)和0. 750 h(中位值:0. 75 h); Cmax分别为(29. 8±5. 99)和(29. 5±5. 72) ng·m L-1;AUC0～t分别为(91. 1±14. 5)和(93. 3±16. 3) h·ng·m L-1; AUC0～∞分别为(92. 6±14. 6)和(94. 7±16. 3)h·ng·m L-1。餐后组受试制剂和参比制剂的血浆中原形沙格列汀主要药动学参数如下:t1/2分别为(3. 84±1. 57)和(3. 90±1. 50) h; Tmax分别为1. 61 h(中位值:1. 50 h)和1. 51 h(中位值:1. 00 h); Cmax分别为(25. 7±7. 41)和(26. 4±4. 61) ng·m L-1; AUC0～t分别为(103±17. 3)和(104±14. 5) h·ng·m L-1; AUC0～∞分别为(105±17. 5)和(106±15. 1) h·ng·m L-1。受试制剂和参比制剂安全性良好,未发生严重不良反应。结论:根据国家药品监督管理局的生物等效性判定标准,受试制剂沙格列汀片和参比制剂安立泽~单次给药在中国健康受试者中安全性均良好,且两制剂生物等效。
        Objective: To evaluate the bioequivalence and safety of saxagliptin table(tested preparation,5 mg) Jiangsu ASK pharmacentical Co.,Ltd.,and Onglyza~table(reference preparation,5 mg,BMS) in Chinese health subjects. Methods: This was a single-center,open-label,randomized,two-period,cross-over pharmacokinetic study. Total of 48 health Chinese health male subjects received saxagliptin tables and Onglyza~tables,including fasting group(24 cases) and postprandial group(24 cases). The following pharmacokinetic parameters were calculated by WinNolin 6. 4 software. Results: Pharmacokinetic and bioequivalence analysis were performed in the blood concentration-time curves of 23 subjects in the fasting group and 21 in the postprandial group. Subjects administered test saxagliptin table and Onglyza~table in the fasting state had t1/2 of(3. 56 ± 1. 52) h and(3. 70 ±1. 28) h,respectively; Tmaxof 0. 587 h(median,0. 5 h) and 0. 750 h(median,0. 75 h),respectively; Cmaxof(29. 8 ± 5. 99) ng·m L-1 and(29. 5 ± 5. 72) ng·m L-1,respectively; an AUC0 ～ tof(91. 1 ± 14. 5) h·ng·m L-1 and(93. 3 ± 16. 3) h·ng·m L-1,respectively; and AUC0 ～ ∞of(92. 6 ± 14. 6) h·ng·m L-1 and(94. 7 ± 16. 3)h·ng·m L-1,respectively. Subjects administered test saxagliptin table and Onglyza~table in the fed state had t1/2 of(3. 84 ± 1. 57) h and(3. 90 ± 1. 50) h,respectively; Tmaxof 1. 61 h(median,1. 50 h) and 1. 51 h(median,1. 00 h),respectively; Cmaxof(25. 7 ± 7. 41) ng·m L-1 and(26. 4 ± 4. 61) ng·m L-1,respectively; AUC0 ～ tof(103 ± 17. 3) h·ng·m L-1 and(104 ± 14. 5) h·ng·m L-1,respectively; and AUC0 ～ ∞of(105 ± 17. 5) h·ng·m L-1 and(106 ± 15. 1) h·ng·m L-1,respectively. The tested preparation and reference preparation were safe,with no serious adverse events observed. Conclusion: According to the criteria for bioequivalence of National Medical Products Administration(NMPA),the tested preparation saxagliptin table and reference preparation Onglyza~table were determined to be both safety in Chinese health subjects,and the two preparations were bioequivalent.

引文

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